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Molecular evolution of early-onset prostate cancer identifies molecular risk markers and clinical trajectories.
Gerhauser C Favero F Risch T Simon R Feuerbach L Assenov Y Heckmann D Sidiropoulos N Waszak SM Hubschmann D
Gerhauser C
Favero F
Risch T
Simon R
Feuerbach L
Assenov Y
Heckmann D
Sidiropoulos N
Waszak SM
Hubschmann D
Citations
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Abstract
Identifying the earliest somatic changes in prostate cancer can give important insights into tumor evolution and aids in stratifying high- from low-risk disease. We integrated whole genome, transcriptome and methylome analysis of early-onset prostate cancers (diagnosis ?55 years). Characterization across 292 prostate cancer genomes revealed age-related genomic alterations and a clock-like enzymatic-driven mutational process contributing to the earliest mutations in prostate cancer patients. Our integrative analysis identified four molecular subgroups, including a particularly aggressive subgroup with recurrent duplications associated with increased expression of ESRP1, which we validate in 12,000 tissue microarray tumors. Finally, we combined the patterns of molecular co-occurrence and risk-based subgroup information to deconvolve the molecular and clinical trajectories of prostate cancer from single patient samples.
Authors
Gerhauser C
Favero F
Risch T
Simon R
Feuerbach L
Assenov Y
Heckmann D
Sidiropoulos N
Waszak SM
Hubschmann D
Urbanucci A
Girma EG
Kuryshev V
Klimczak LJ
Saini N
Stutz AM
Weichenhan D
Bottcher LM
Toth R
Hendriksen JD
Koop C
Lutsik P
Matzk S
Warnatz HJ
Amstislavskiy V
Feuerstein C
Raeder B
Bogatyrova O
Schmitz EM
Hube-Magg C
Kluth M
Huland H
Graefen M
Lawerenz C
Henry GH
Yamaguchi TN
Malewska A
Meiners J
Schilling D
Reisinger E
Eils R
Schlesner M
Strand DW
Bristow, Robert G
Boutros PC
von KC
Gordenin D
Sultmann H
Brors B
Sauter G
Plass C
Yaspo ML
Korbel JO
Schlomm T
Weischenfeldt J
Favero F
Risch T
Simon R
Feuerbach L
Assenov Y
Heckmann D
Sidiropoulos N
Waszak SM
Hubschmann D
Urbanucci A
Girma EG
Kuryshev V
Klimczak LJ
Saini N
Stutz AM
Weichenhan D
Bottcher LM
Toth R
Hendriksen JD
Koop C
Lutsik P
Matzk S
Warnatz HJ
Amstislavskiy V
Feuerstein C
Raeder B
Bogatyrova O
Schmitz EM
Hube-Magg C
Kluth M
Huland H
Graefen M
Lawerenz C
Henry GH
Yamaguchi TN
Malewska A
Meiners J
Schilling D
Reisinger E
Eils R
Schlesner M
Strand DW
Bristow, Robert G
Boutros PC
von KC
Gordenin D
Sultmann H
Brors B
Sauter G
Plass C
Yaspo ML
Korbel JO
Schlomm T
Weischenfeldt J
Description
Date
2018
Publisher
Collections
Keywords
Type
Article
Citation
Gerhauser C, Favero F, Risch T, Simon R, Feuerbach L, Assenov Y, et al. Molecular evolution of early-onset prostate cancer identifies molecular risk markers and clinical trajectories. Cancer Cell. 2018 Dec 10;34(6):996-1011 e8.